NM_001010858.3:c.295G>C

Variant names:

• chr1-228487783-G-C
• rs938361737
• NM_001010858.3:c.295G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001010858.3(RNF187):​c.295G>C​(p.Ala99Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A99T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF187 NM_001010858.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 0 publications found

Genes affected

RNF187 (HGNC:27146): (ring finger protein 187) Enables ubiquitin-protein transferase activity. Involved in positive regulation of transcription, DNA-templated; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein ubiquitination. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000293430 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26526105).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010858.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF187	NM_001010858.3	MANE Select	c.295G>C	p.Ala99Pro	missense	Exon 1 of 4	NP_001010858.2	Q5TA31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF187	ENST00000305943.9	TSL:1 MANE Select	c.295G>C	p.Ala99Pro	missense	Exon 1 of 4	ENSP00000306396.9	Q5TA31
	ENSG00000293430	ENST00000739614.1		n.658-6791C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Benign	0.076	N
MetaRNN	Benign	0.27	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.055
PrimateAI	Pathogenic	0.91	D
Sift4G	Benign	0.30	T
Polyphen		0.91	P
Vest4		0.18
MVP		0.64
GERP RS		2.2
PromoterAI		-0.056	Neutral
Varity_R		0.11
gMVP		0.36
Mutation Taster		=278/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs938361737; hg19: chr1-228675484;